Sesamol derivative reduces atherosclerosis in laboratory study

An article published online on December 23, 2010 in the American Heart Association journal Arteriosclerosis, Thrombosis, and Vascular Biology reports the finding of Ohio State University researchers of an antiatherosclerotic benefit for INV-403, a modified form of sesamol, which is a phenolic component of lignans found in sesame seeds.

Sanjay Rajagopalan, MD and his associates tested the effects of the compound in rabbits that develop elevated lipids and atherosclerosis. Ten rabbits were given a high-cholesterol diet for 6 weeks, followed by 12 weeks of the diet with or without INV-403. Magnetic resonance imaging assessment of the abdominal aorta at the beginning of the treatment period and after 6 and 12 weeks of supplementation evaluated atherosclerosis progression.

After 6 weeks of treatment with INV-403, atherosclerotic plaque volume was significantly reduced compared with plaque measured in animals that did not receive the compound, and by 12 weeks a greater decline in plaque progression was observed in the treated animals. Examination of the aorta found a decrease in immune system cells known as CD68+ cells and less lipid accumulation in those that received the sesamol derivative. INV-403 also improved vascular function, lowered systemic and plaque oxidative stress, and inhibited the expression of proinflammatory genes and DNA-binding of nuclear factor–kappa-beta (NF-kB), which is involved in the regulation of inflammatory processes. Inhibition of NF-kB was not due to antioxidant effects or nitric oxide production.

“INV-403 exerts important vascular protective effects in a model of severe hyperlipidemia atherosclerosis,” the authors conclude. “These findings may have implications for further testing of modified forms of sesame lignans in the treatment of atherosclerosis.”

December 22, 2010

Bad news for junk food junkies

A team led by Amy L. Anderson, PhD of the University of Maryland analyzed data from 2,582 participants in The Health, Aging and Body Composition Study of American adults aged 70 to 79 upon enrollment. Dietary questionnaires completed during the second year after enrollment were used to group the subjects' diets into the following 6 categories based on predominant choices: healthy foods, high-fat dairy products, meat, fried foods and alcohol, breakfast cereal, refined grains, and sweets and desserts.

During the follow-up period of up to 10 years, 739 men and women died. Those whose diets consisted of healthy food, characterized by a higher intake of low-fat dairy products, fruit, whole grains, poultry, fish and vegetables, and reduced consumption of meat, fried foods, sweets, high-calorie drinks and added fat, had a significantly lower risk of dying than those whose diets were dominated by high-fat dairy products (which included such foods as ice cream, cheese and whole milk); meat, fried foods and alcohol, or sweets and desserts. Adjusted analysis of the data found a 40 percent greater risk of dying among those who consumed relatively higher amounts of high-fat dairy products, and a 37 percent greater risk for those whose diets were characterized by a lot of sweets.

The current study's findings are in line with those that indicate a positive impact on survival for the Mediterranean or plant-based diets. "Because a substantial percentage of older adults in this study followed the 'Healthy foods' dietary pattern, adherence to such a diet appears a feasible and realistic recommendation for potentially improved survival and quality of life in the growing older adult population," the authors conclude.

The International Osteoporosis Foundation Regionals--1st Asia-Pacific Regional Osteoporosis Meeting held in Singapore December 10-13, 2010 was the site of the presentation concerning a study conducted in New Delhi, India which found widespread vitamin D deficiency in older men and women with hip fracture.

S. K. Sahoo, D. K. Dhanwal and V. K. Gautam at Maulana Azad Medical College matched 90 patients admitted to Lok Nayak Hospital with hip fracture with a similar number of control subjects who did not have fractures. Blood samples were analyzed for serum 25-hydroxyvitamin D, intact parathyroid hormone, calcium, albumin and other factors.

Vitamin D deficiency, defined as a serum 25-hydroxyvitamin D level of less than 250 nanograms per deciliter, occurred in 76.7 percent of those with hip fracture and 32.3 percent of the control participants. Calcium and albumin levels were also significantly lower in the hip fracture group. Sixty-nine percent of the hip fracture group had serum parathyroid levels above 54 picograms per deciliter indicative of secondary hyperparathyroidism (associated with vitamin D and calcium insufficiencies) compared with 42.2 percent of the controls.

Reduced vitamin D levels have been associated with the development of osteoporosis as well as diminished muscle strength and other conditions. Because the vitamin is formed in the skin in response to sun exposure, pigment levels and traditional clothing worn by the Indian population could make deficiency more common. “Our results indicate that about three-fourths (76.7%) of hip fracture patients had vitamin D deficiency, whereas about two-thirds had secondary hyperparathyroidism suggesting that these conditions may be closely associated with hip fracture in elderly people” the authors conclude.

In Neurorehabilitation and Neural Repair, Fernando Gomez-Pinilla, PhD, and his colleagues at the University of California, Los Angeles report the effects of CNB-011 in a rat model of traumatic brain injury. In addition to reversing decreases in memory and locomotion, Dr Gomez-Pinilla and his associates found that the compound helped maintain nerve cell connections as well as signaling pathways necessary for nerve cell survival.

In another article, which appears in the January, 2011 issue of the Journal of Neurochemistry, Paul A Lapchak, PhD of Cedars-Sinai Medical Center in Los Angeles, and David Schubert and Pamela Maher of the Salk Institute for Biological Studies report that CNB-011 was effective at improving the behavioral outcome in an animal model of stroke even when administered one hour after the event, which compares to the therapeutic window for the current human stroke treatment of choice, TPA.

CNB-011 was developed by Drs Schubert and Maher via a new drug discovery paradigm that starts with natural products and proceeds to the identification of derivatives that offer protection against neurologic damage. "To test the prediction that drugs from our new drug discovery scheme will work in multiple models of CNS disease and trauma we undertook a series of experiments to assay the drugs in collaboration with researchers at Cedars-Sinai and UCLA, who are leaders in the fields of stroke and TBI, respectively, and appreciate the potential for therapeutics based on natural products and their derivatives," Dr Schubert stated.

December 13, 2010

Drug could reverse decline in immune function that accompanies aging

The January, 2011 issue of the journal Clinical Immunology will publish the discovery of researchers at the University of California, San Francisco (UCSF) of the ability of the drug lenalidomide to restore immune function in older men and women. An imbalance of the immune system can result in a decreased ability to fight infection and increased inflammation, both of which can be detrimental to well-being and longevity.

Edward J. Goetzl, MD, who is UCSF's Director of Allergy and Immunology Research, sought an agent that could elevate levels of the protective immune cytokines interferon-gamma and interleukin-2 in older individuals in which the cytokines had declined. Lenalidomide is a derivative of thalidomide, which is currently being used to treat some cancers that are associated with a decrease in interleukin-2. “Our job was to find a therapy that not only works, but does so at a dose range with no side effects,” Dr Goetzl stated.

Dr Goetzl and his colleagues studied the effects of lenalidomide in 13 healthy seniors who were matched for gender and race with healthy 21 to 40 year old subjects. They found that very low amounts of the drug stimulated interleukin-2 by 7-fold in the young subjects, and by 120-fold in the older participants, resulting in restoration of the cytokine to youthful levels for five days. Older subjects who received the drug also experienced a 6-fold increase in gamma-interferon and improved T-cell function.

“No one’s really talking about longevity and lifespan now, but about ‘health span,’” Dr Goetzl remarked. “If, at age 50, your cytokine levels are the same as they were at 25, you’ll probably stay healthy as you age. But if they’re heading downhill, we need to do something about it. If you could take a low-dosage pill with no side effects, wouldn’t you do it?”

December 13, 2010

Estrogen-only replacement may have a protective benefit against breast cancer

Research conducted at the University of British Columbia in Vancouver, reported at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium held December 8-12, 2010, reveals a protective effect for estrogen given alone against the risk of breast cancer.

University of British Columbia School of Population and Public Health clinical professor Joseph Ragaz, MD, and his associates note that while the body’s own estrogen can fuel breast cancer growth, adding estrogen replacement without progestins (which protect against uterine cancer) may help prevent breast cancer according to an analysis of data from the Women’s Health Initiative (WHI) trials of hormone replacement therapy (HRT). The trials evaluated the effects of estrogen plus progestin in women who had an intact uterus and estrogen alone in women who had undergone hysterectomies.

While the WHI findings associated the estrogen-progestin combination with an increased risk of breast cancer, the use of estrogen alone was associated with a 20 percent lower risk of the disease compared with the placebo group, and those without a strong family history of breast cancer experienced a 32 percent lower risk.

"Our analysis suggests that, contrary to previous thinking, there is substantial value in bringing HRT with estrogen alone to the guidelines,” Dr Ragaz stated. “The data show that for selected women it is not only safe, but potentially beneficial for breast cancer, as well as for many other aspects of women's health. These findings should intensify new research into its role as a protective agent against breast cancer."

"Our conclusion, based on the data presented, should enhance considerations for an early approval of HRT based on estrogen-alone for the majority of selected women suffering with menopausal symptoms and galvanize new research on HRT to define the optimum regimens for individual women," he added.

December 10, 2010

Vitamin A supplements save children’s lives in developing countries

The latest issue of The Cochrane Reviews published the results of a meta-analysis which found that supplementation with vitamin A was associated with a reduction in mortality from all causes in children in the developing world. The vitamin is necessary for healthy immune function, vision and other body functions.

For their review, researchers from Aga Khan University Hospital in Karachi, Pakistan selected 17 trials comparing supplementation with the dose of vitamin A recommended by the World Health Organization to a placebo or no treatment in 194,795 children between the ages of 6 months and 5 years. Three thousand five hundred thirty-six deaths were documented among the participants. For those who received vitamin A capsules, a 24 percent lower risk of death from all causes occurred compared with those who did not receive the vitamin. In other meta-analyses, vitamin A supplementation was associated with a lower risk of dying from diarrhea and less morbidity from the condition.

“Giving vitamin A is associated with a reduction in the incidence of diarrhea and measles, as well as the number of child deaths due to these diseases," noted Zulfiqar Bhutta, who is the Chairman of the Division of Women and Child Health at Aga Khan University. "However, the effects of supplementation on disease pathways are not well understood, so this could be a focus for further studies."

"Fortification, dietary diversification, food distribution programs and horticultural developments such as home gardening and biofortification may provide more permanent relief," he suggested. "For example, vitamin A content could be increased in staples such as rice or growers may aim to promote use of biofortified foods such as orange sweet potato."

December 8, 2010

Iron dysregulation could be behind numerous diseases

Professor Douglas B. Kell of the University of Manchester proposes a link between poorly-bound iron and a number of diseases in a review published online on December 8, 2010 in the Archives of Toxicology.

In his introduction, Dr Kell explains that poorly liganded iron, which more freely reacts with other molecules, results in the production of damaging hydroxyl radicals that contribute to a number of degenerative diseases. Iron chelators, found in richly pigmented fruit and vegetables as well as green tea, bind iron tightly and prevent this reaction. By increasing the intake of these foods, the risk of a number of diseases could be reduced, including stroke, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, Huntington’s disease, Friedreich’s ataxia, age-related macular degeneration, prion diseases such as transmissible spongiform encephalopathies and Creutzfeldt-Jakob disease, atheroscerosis, sepsis and septic shock, toxic reactions and other conditions.

The article is the first to link such apparently diverse diseases with iron dysregulation. Dr Kell notes that “some molecules—both nutrients/natural products and pharmaceutical agents—can act as both antioxidants and iron chelators; these are likely to be especially useful in minimising the damage from toxicants of many kinds.” He lists anthocyanins, epigallocatechin-3-gallate from green tea, curcumin, eugenol, quercetin and melatonin as nonpharmaceutical, nutritive iron chelators.

"Much of modern biology has been concerned with the role of different genes in human disease,” Dr Kell remarked. "The importance of iron may have been missed because there is no gene for iron as such. What I have highlighted in this work is therefore a crucial area for further investigation, as many simple predictions follow from my analysis. If true they might change greatly the means by which we seek to prevent and even cure such diseases."

The studies examined the incidence of cancer in type 2 diabetic populations. In the first study published in Diabetes Care, Italian researchers compared 112 insulin-treated diabetics who developed cancer with 370 diabetics treated with insulin who did not have the disease. The use of metformin was found to be associated with a 54 percent lower adjusted risk of cancer. “The reduction of cancer risk could be a further, relevant reason for maintaining metformin in insulin-treated patients,” the authors conclude.

In the second Diabetes Care article, researchers in Hong Kong report that an association between a lower risk of cancer and metformin was stronger among diabetics with low high density lipoprotein (HDL) cholesterol. Subjects who had low HDL and were nonusers of metformin had a 5.75 times greater risk of cancer compared to metformin users with higher HDL levels.

The study described in Cancer Epidemiology, Biomarkers & Prevention matched 393 peri- and postmenopausal Danish women with breast cancer and type 2 diabetes with 3930 diabetic controls. Subjects who used metformin for at least one year had a 19 percent lower adjusted risk of breast cancer than those who did not use the drug. “This study supports the growing evidence of a role for metformin in breast cancer chemoprevention,” the authors write.

Metformin may decrease cancer risk by decreasing insulin levels and reducing cell proliferation. In previous research, metformin use has been associated with lower cancer-related mortality. Future studies will further define the protective benefit of this drug in other populations.

December 3, 2010

Earlier mortality risk rises with body mass index

A large analysis reported in the December 2, 2010 issue of the New England Journal of Medicine confirms the relationship between being overweight or obese and a greater risk of dying from all causes during a median 10 years of follow-up.

Amy Berrington de Gonzalez of the National Cancer Institute, along with a team of colleagues from the United States, Australia and other nations, pooled data from 19 prospective studies totaling 1,462,958 white male and female participants between the ages of 19 and 84. Body mass index (BMI), calculated by dividing a person’s weight in kilograms by the square of their height in meters, was determined for all subjects. The participants were followed for periods that ranged from a maximum of 7 to 28 years, during which 160,087 deaths occurred.

Median BMI was 26.2 upon enrollment. Compared with women whose body mass index was between 22.5 and 24.9, having a BMI of 25 to 29.9 was associated with a 13 percent greater risk of death over follow-up. This risk rose with increasing body mass index categories, with women whose BMI was 40 to 49.9 having 2 1/2 times the risk of death from all causes than those with a BMI of 22.5 to 24.9. Risks among men were similar. Although a smaller increase in mortality risk was also observed for those whose BMI was lower than 20, the authors suggest that the finding was in part caused by preexisting disease, noting that the association weakened after 15 years of follow up .

“In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality,” the authors conclude. “All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.”

November 29, 2010

Reduced folate levels linked with hearing loss

In December 2010 issue of the journal Otolaryngology – Head and Neck Surgery, Akeem Lasisi and his colleagues at the University of Ibadan in Nigeria report an association between decreased serum levels of the B vitamin folate and a greater incidence of hearing loss in older men and women.

The study included 126 healthy participants over the age of 60 residing in Nigeria. Potential subjects who had conditions that could contribute to hearing loss, such as exposure to noise or drugs known to affect hearing, were excluded. Blood samples were analyzed for serum folate and vitamin B12, and audiology tests were conducted.

Participants with a normal ability to hear speech frequencies had average serum folate levels of 412.3 nanomoles per liter compared to 279.1 nanomoles per liter among those with speech frequency hearing loss. Those with a normal ability to hear high frequencies had levels that averaged 426.3 nanomoles per liter, while participants with high frequency loss had levels similar to those with speech frequency loss.

While vitamin B12 levels were not found to have a significant protective effect against the loss of speech frequencies, among those with a normal ability to hear high frequencies, values averaged 47.4 picomoles per liter compared to 41.3 picomoles per liter in subjects with high frequency losses. “We found correlation between high frequency hearing loss and low serum vitamin B12, although serum vitamin B12 seemed to be affected by increasing age hence the correlation with vitamin B12 was not found to be significant after adjusting for age,” the authors remark.

"Based on our research, age-related hearing loss may be associated with poor micronutrient status,” Dr Lasisi concluded. “The role of folate in cellular metabolism, the nervous system, and vascular function are important for the auditory system.”

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